Group membership modulates the hold-up problem: an event-related potentials and oscillations study.

This paper investigates the neural mechanism that underlies the effect of group identity on hold-up problems. The behavioral results indicated that the investment rate among members of the in-group was significantly higher than that of the out-group. In comparison to the NoChat treatment, the Chat treatment resulted in significantly lower offers for both in-group and out-group members. The event-related potentials (ERP) results demonstrated the presence of a distinct N2 component in the frontal midline of the brain when investment decisions were made for both in-group and out-group members. During the offer decision-making stage, the P3 peak amplitude was significantly larger when interacting with in-group members compared to the out-group members. The event-related potentials oscillations (ERO) results indicated that when investment decisions were made for in-group members in the NoChat treatment, the beta band (18-28 Hz, 250-350 ms) power was more pronounced than when decisions were made for out-group members. In the NoChat treatment, offer decisions for in-group members yielded a more pronounced difference in beta band (15-20 Hz, 200-300 ms) power when compared to out-group members. Evidence from this study suggests that group identity can reduce the hold-up problem and corroborates the neural basis of group identity.

Group identity modulates bidding behavior in repeated lottery contest: neural signatures from event-related potentials and electroencephalography oscillations.

A contest usually involves expenditures, termed "overbidding," exceeding the theoretical Nash equilibrium. A considerable number of studies have shown that group identity can affect decision-making and competitive behavior, thus providing a new perspective on alleviating the overbidding problem. How group identity influences brain activity when competitors bid in different groups is not yet clear, however. In this study, we implemented group identity manipulation into the lottery contest game and we recorded behavioral and electroencephalography (EEG) data at the same time. Two experimental treatments were conducted to study the effect of group identity on bidding behavior. The event-related potentials (ERP) and event-related oscillations (ERO) techniques were utilized to explore brain activity differences caused by participants' different bidding behaviors under in-group and out-group conditions. Behavioral results showed that individual expenditure was significantly lower when bidding with in-group opponents than with out-group opponents. Analyses of EEG results revealed that compared to in-group conditions, greater N2 amplitudes and theta power were found under out-group conditions. To extend previous studies, we performed supplementary analysis to explore whether enhancement of group identity had effects on conflict alleviation. Behavioral results indicated that individual expenditure was significantly lower after enhancing group identity when bidding with in-group, and EEG results showed more negative N2 amplitudes, smaller P3 amplitudes and larger theta power after enhancing group identity. Collectively, these findings indicate that group identity modulated bidding behavior, and they provide insight into a mechanism to de-escalate group conflict by enhancing group identity.

An optimized method for neutron dose evaluation based on24Na activity distribution in the human body.

The neutron dose resulting from external irradiation can be evaluated by measuring the counts of characteristicγrays produced by24Na in the human body. The detection geometry with the highest detection efficiency for measuring the whole-body24Na activity has not been studied. In this work, the MCNP code is used to calculate the spatial distribution of24Na in the human body irradiated by neutrons with different energies in different irradiation geometries. The fluence distribution of24Na characteristicγrays on the body surface is calculated. The counts of24Na characteristicγrays induced by monochromatic neutron irradiation are simulated to fit the scenarios of neutron irradiation by a continuous energy spectrum neutron. When the spontaneous neutrons from252Cf with 1Gy dose irradiate the human body, (3.63-4.35) × 1010 24Na atoms are produced. The lower detection limit for the neutron absorption dose is reduced from ∼100 to less than 1 mGy when the radiation detector is placed over the back of the human body close to the liver. The relative error between the measured counts of24Na characteristic γ rays caused by252Cf neutron irradiation and the counts fitted by monochromatic neutron irradiation data is less than 5.7%. The neutron dose received from a continuous energy spectrum neutron can be acquired quickly and accurately by weighted summing of the data for monochromatic neutron irradiations calculated in this paper, which is more convenient and practical than the previous method.

Progress of neoadjuvant therapy for high-risk prostate cancer in the era of novel hormonal therapy / 现代泌尿外科杂志

In the past, the use of neoadjuvant androgen deprivation therapy (ADT) for prostate cancer did not exhibit survival benefits and was not recommended by the practicing guidelines. In recent years, with the emergence of novel hormonal therapeutics such as Abiraterone, Enzalutamide, Apalutamide and Darolutamide, the interest for neoadjuvant therapy has been reignited. Here, we summarize the four categories of neoadjuvant therapy with new hormonal agents, and discuss how to evaluate the efficacy and explore the molecular mechanism after neoadjuvant therapy.

Ideal cardiovascular health and mortality: pooled results of three prospective cohorts in Chinese adults / 中华医学杂志(英文版)

BACKGROUND@#Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps.@*METHODS@#A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis.@*RESULTS@#During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed.@*CONCLUSIONS@#ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.

Therapeutic effect of small extracellular vesicles derived from mesenchymal stem cells on retinal light injury and its mechanism / 中华实验眼科杂志

Objective:To investigate the effect of small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) in mouse model of retinal light injury and the possible mechanism.Methods:Human umbilical cord derived MSCs were identified by flow cytometry.Supernatants of passage 3-5 MSCs were collected.sEVs were harvested by ultracentrifugation and were identified by transmission electron microscopy.Sixty-five healthy female SPF-grade BALB/c mice aged 8-10 weeks were randomly divided into normal group (17 mice), phosphate buffered saline (PBS) group (24 mice) and sEVs group (24 mice). Mice in PBS and sEVs groups were intravitreally injected with 2 μl of PBS and sEVs, respectively, and were exposed to 930 lx blue light for 6 hours.No intervention was administered to the normal group.Three days after lighting, mice retinal structure was observed by hematoxylin-eosin staining.Apoptotic retinal cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Retinal function was tested by electroretinogram.Differentially expressed mRNAs between PBS group and sEVs group were assayed by mRNA transcriptome sequencing and were analyzed through KEGG cluster analysis.The differential mRNAs were verified via real-time quantitative PCR.The study protocol was approved by the Animal Ethics Committee of Tianjin Medical University Eye Hospital (No.TJYY20201221035).Results:MSCs were positive for CD90 and CD105, negative for CD34 and CD45.The extracted MSC-sEVs showed a bilayer membrane vesicle with a diameter of 80-140 nm.Hematoxylin-eosin staining showed the arrangement of photoreceptor nuclei was disordered in outer nuclear layer in PBS group.The disorder of photoreceptor nuclei arrangement of sEVs group was slighter than that of PBS group.The apoptotic cell number of sEVs group was (14.60±4.04)/visual field, which was lower than (24.00±8.52)/visual field of PBS group, with a statistically significant difference ( t=2.37, P<0.05). The a-wave amplitude of sEVs group was (64.38±16.70)μV, which was higher than (16.78±6.37) μV of PBS group, showing a statistically significant difference ( P<0.05). The b-wave amplitudes of PBS and sEVs groups were (132.40±39.41) μV and (154.86±34.08) μV, respectively, which were lower than (338.38±27.41) μV of normal group, and the differences were statistically significant (both at P<0.05). A total of 110 differentially expressed mRNAs were detected.There were 109 downregulated mRNAs in sEVs group.Differentially expressed mRNAs were mainly inflammation- and immune-related pathways.PCR showed that the expression level of C-C motif chemokine ligand 2, C-C motif chemokine receptor 2, leukotriene B4, leukocyte Ig-like receptor A6 and interleukin-1β in sEVs group were significantly decreased in comparison with PBS group (all at P<0.05). Conclusions:MSC-sEVs can ameliorate blue light-induced retinal structural and functional damage.The protective effect may be achieved through inhibiting inflammatory response.

Transcranial direct current stimulation of the LTPJ shifts the agent's behaviors in repeated hold-up game.

The Hold-up problem is very common in transactions with specific investment in incomplete contractual relationships, which is affected by human trusting, cooperative, altruistic behavior. Recent neuroscience studies have shown that TPJ plays an important role in social cognition and prosocial decision-making. However, most of the studies have focused on RTPJ in the right hemisphere, while few studies have focused on LTPJ in the left hemisphere. The purpose of this study is to modulate the excitability of LTPJ through transcranial direct current stimulation (tDCS) and to explore the effects of LTPJ on the investment and offer behavior of participants in the repeated hold-up game. Our results showed that cathodal stimulation significantly improved the investment rate of participants in the repeated hold-up game compared with sham stimulation. One possible explanation is that the change of LTPJ activity caused by cathodal stimulation may reduce the participants' inference ability of the others' intention, thus reducing the participants' betrayal aversion behavior, so that the participants will not reduce their investment behavior in the repeated game.

MicroRNA-629-3p Promotes Interleukin-13-Induced Bronchial Epithelial Cell Injury and Inflammation by Targeting FOXA2.

OBJECTIVE: Asthma is a chronic pulmonary inflammatory disease. MicroRNA (miR)-629-3p expression is reported to be up-regulated in the sputum of asthma patients. Nonetheless, miR-629-3p's role and mechanism in asthma remain largely unknown. This study is aimed at exploring miR-629-3p's role in regulating the injury and inflammation of bronchial epithelial cells. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the expression levels of miR-629-3p and forkhead box a2 (FOXA2) mRNA in 16HBE cells treated with interleukin-13 (IL-13). 16HBE cell viability was evaluated using the cell counting kit-8 (CCK-8) assay, and cell apoptosis was analyzed by a flow cytometer. The levels of C-C motif chemokine ligand 11 (CCL11), C-C motif chemokine ligand 26 (CCL26), C-C motif ligand 2 (CCL-2)/mono-cyte chemotactic protein-1 (MCP-1), interleukin-1 beta (IL-1b), and interleukin 6 (IL-6) in 16HBE cell supernatant were detected through enzyme-linked immunosorbent assay (ELISA). The downstream target genes of miR-629-3p were predicted through bioinformatics. Besides, the targeted relationship between miR-629-3p and FOXA2 mRNA 3'-UTR was verified by dual-luciferase reporter gene assay. Western blot was utilized to determine the regulatory effects of miR-629-3p on the expression of FOXA2 protein in 16HBE cells. RESULTS: MiR-629-3p expression was significantly enhanced in IL-13-stimulated 16HBE cells while the FOXA2 mRNA and protein levels were significantly down-regulated. The transfection of miR-629-3p mimics inhibited 16HBE cells' viability, and promoted the apoptosis and the secretion of chemokines CCL11, CCL26, CCL-2/MCP-1, IL-1b, and IL-6 of 16HBE cells, whereas inhibiting miR-629-3p had the opposite effects. Moreover, FOXA2 was identified as a downstream miR-629-3p target, and its overexpression reversed the effects of the miR-629-3p on 16HBE cells. CONCLUSION: MiR-629-3p promotes IL-13-induced 16HBE cells' injury and inflammation by targeting FOXA2.

Value of the biomarkers derived from cerebrospinal fluid in the diagnosis of Alzheimer disease / 中华检验医学杂志

Alzheimer disease (AD) is a neurodegenerative disease in the elderly. Early intervention is the only reliable means to delay the progress of the disease. Referring to the diagnostic criteria of AD, this paper summarizes and analyzes the representative literatures of various AD biomarkers derived from cerebrospinal fluid in recent years, and reviews the efficacy of various cerebrospinal fluid biomarkers in the diagnosis and differential diagnosis of AD. Results show that CSF Aβ42, Aβ42/Aβ40, T-tau, p-tau, Aβ42/p-tau, growth-associated protein 43, synaptosomal-associated protein 25, neurogranin and visinin-like protein-1 are of great value in the diagnosis and differential diagnosis of AD. The above CSF biomarkers can be used in the diagnosis and differential diagnosis of AD. The laboratory should select appropriate AD CSF biomarkers according to its own conditions in daily laboratory works.

Analysis of clinical characteristics and genetic susceptibility of steroid-induced ocular hypertension in patients with uveitis / 中华眼底病杂志

Objective:To observe the clinical characteristics of steroid-induced ocular hypertension (SIOH) in patients with uveitis, and explore the relationship between its clinical phenotype and gene polymorphism.Methods:A retrospective case-control study. From July 2019 to December 2020, 576 patients with uveitis who were treated with glucocorticoid eye drops in Tianjin Medical University Eye Hospital were included in the study. Among them, there were 175 confirmed glucocorticoid responders (SRs) and 401 glucocorticoid non-responders (NRs). Seventy cases of SRs (age ≥18 years) using 1 % prednisone acetate eye drops were selected as the experiment group and 64 cases of NRs were selected as the control group. The polymorphism of rs2523864 and rs3873352 of human leukocyte antigen complex group ( HCG) 22 gene were detected by Sanger sequencing. To observe the clinical characteristics of SIOH after the use of glucocorticoid eye drops, and the correlation between rs2523864 and rs3873352 and the occurrence of SIOH. Differences among groups were compared with the Chi-square test or Fisher's exact test. The correlation between the occurrence of SIOH and the range of intraocular pressure increases after glucocorticoid use and the rs2523864 and rs3873352 loci were compared using the odds ratio ( OR) and its 95% confidence interval ( CI). Results:SIOH occurred in 175 (30.4%, 175/576) of 576 patients. Among them, there were 96 males (54.9%, 96/175) and 79 females (45.1%, 79/175); the average age was 33.64±17.40 years. Steroid high responders (HRs) and steroid moderate responders (MRs) were 58 (33.1%, 58/175) and 117 (66.9%, 117/175) cases. The medication time for the increase in intraocular pressure in MRs that was 33 (19, 56) days, and in HRs that was 28 (14, 36) days, the difference of which was significant ( Z=-1.999, P=0.046). No differences were found in daily doses of ocular hypertension induced by 1% prednisone acetate eye drops between MRs which was 4.24 (3.46, 4.66) drops/day and HRs that was 4.32 (3.84, 5.36) drops/day ( Z=-1.676, P=0.094). The genotype and allele frequency distribution of the rs3873352 locus in the case group and HRs group were significantly different from those in the control group ( P<0.05). The intraocular pressure with rs3873352 GG genotype after the medication was higher than that with GC and CC genotype ( Z=2.855, 2.628; P=0.013, 0.026), whereas there was no significant difference between different genotypes of rs2523864 ( Z=3.580, P>0.05). Genetic model analysis revealed the risk of SIOH in rs3873352 G allele carriers (GG+GC) was 2.048 times that of non-G allele carriers ( OR=2.048, 95% CI: 1.027-4.081, P=0.041). The genotype and allele frequency of rs2523864 locus showed no significant difference between different group ( P>0.05). Conclusions:After the use of glucocorticoid eye drops, HRs have an earlier increase in intraocular pressure than MRs. HCG22-rs3873352 gene polymorphism is related to the occurrence of SIOH, GG genotype increases the risk of SIOH, and G allele is a risk gene for SIOH.

Study on the application of continuous nursing led on the theory of interactive standard theory after heart transplantation / 中国实用护理杂志

Objective:To explore the application research of continuity nursing based on the interactive reaching standard theory after heart transplantation.Methods:The clinical data of 104 patients after heart transplantation in Nanjing Hospital Affiliated to Nanjing Medical University (Nanjing First Hospital) from June 2012 to June 2020 were collected for retrospective study. According to the file order, they were divided into the control group and the experimental group with 52 cases in each group. The control group took regular nursing care, and the experimental group took continuation nursing based on the interactive standard theory on the basis of the control group. The intervention continued for 24 weeks. The compliance behavior, psychological state and other indexes were compared between two groups.Results:The scove of Positive and Negative Affect Scale: after 12 weeks and 24 weeks of nursing, the experimental group′s positive emotion scores (27.71 ± 4.42, 35.11 ± 4.19) were higher than those of the control group (24.45 ± 4.03, 28.87 ± 4.36). The negative emotional scores (24.52 ± 3.71, 16.66 ± 2.28) were lower than those of the control group (28.84 ± 4.14, 23.31 ± 3.46), the differences were statistically significant ( t=5.60, 11.57, P<0.05). After 12-week and 24-week nursing, the experimental group′s health knowledge level score (44.12 ± 4.43, 53.64 ± 4.55) , self-care skills score(35.35 ± 4.01, 44.78 ± 4.22) , self-responsibility score (21.15 ± 2.38, 26.11 ± 1.44) , and self-concept score (18.56 ± 6.25, 23.58 ± 2.58) were higher than the control group (37.78 ± 4.52 and 45.56 ± 5.13, 31.11 ± 3.64 and 36.65 ± 3.91, 18.82 ± 2.46 and 22.35 ± 1.29, 15.96 ± 4.10 and 18.12 ± 3.10), the differences were statistically significant ( t values were 2.51-14.03, P<0.05). Conclusions:Continuing care led by the interactive standard theory can improve the health literacy of patients after heart transplantation, relieve negative emotions, promote post-traumatic growth, enhance self-management capabilities, establish compliance behaviors, and improve heart function.

Practice and thinking of the multi-district hospital management under the new pattern of national regional medical center / 中华医院管理杂志

The authors took the management practice of " one hospital with multiple districts" in Children′s Hospital Affiliated of Zhengzhou University as the research object, analyzed the main problems and challenges faced by the multi-district hospital management under the new pattern of national regional medical center. Through coordinating the hospital′s strategic planning and the development of discipline layout, building an integrated management system, improving the level of homogeneous service and other key countermeasures, the hospital has significantly improved its management efficiency and operation efficiency, and the medical service capacity of each district has developed in a balanced way. It could give full play to the pilot value for the construction of national regional medical center, hoping to provide reference for hospital administrators.

Expression and determination of biomarkers in diabetic retinopathy / 中华实验眼科杂志

Diabetic retinopathy (DR) is a kind of common vascular complications in diabetes and one of the leading causes of irreversible blindness.It is characterized by leaky retinal vasculature, neovascularization and fiber membrane proliferation.Although there are various DR treatments, most of them aim at middle and late stage of the disease and have limited efficacy.Therefore, early diagnosis and precise treatment of DR are important.In recent years, the research of biomarkers related to DR has developed rapidly, which plays an important role in the risk assessment and early intervention of the disease.Nowadays, classic biomarkers such as HbA1c have been widely used in clinical practice.With the further study on DR, inflammatory biomarkers and angiogenesis-related biomarkers have been found to be closely related to the occurrence and development of the disease.At the same time, with the progress of modern technology, advanced equipment have built a broad platform for the exploration of DR biomarkers.Omics biomarkers, imaging biomarkers and artificial intelligence have become the focus of research and made important contributions to the early treatment of DR.This article summarized the key progress related to the DR biomarkers research to provide new clinical strategies in the efficient prevention, control and treatment of DR.

Regulatory role of non-coding RNA in the pathogenesis of uveitis and future perspectives / 中华实验眼科杂志

Non-coding RNA (ncRNA) is a type of RNA that has multiple biological functions but is not translated into proteins.Uveitis, a common blindness-causing disease, is susceptible to relapse and difficult to treat, but its pathogenesis is not completely elucidated.Recent studies have shown that ncRNA plays an important role in the pathogenesis of human uveitis and rabbit experimental autoimmune uveitis.ncRNAs participate in the pathogenesis of uveitis by regulating important signaling pathways related to immunity, the immune response of T lymphocytes or antigen-presenting cells, and the secretion of inflammatory factors, so targeting some ncRNAs is of certain value for the treatment of uveitis.The single nucleotide polymorphisms and copy number variation of ncRNA are highly correlated with the genetic susceptibility of uveitis.Therefore, ncRNA may become a biomarker for the diagnosis and prognosis of uveitis and targeting ncRNA may become a new treatment strategy in uveitis.The regulatory roles of microRNA and long non-coding RNA in the pathogenesis of uveitis were reviewed in this article.

Therapeutic effect of anti-IL-12/IL-23 p40 on experimental autoimmune uveitis and its mechanism / 中华实验眼科杂志

Objective:To explore the therapeutic effect of anti-interleukin (IL)-12/IL-23 p40 antibody on experimental autoimmune uveitis (EAU) and its mechanism.Methods:Sixty-six SPF female C57BL/6N mice aged 6-8 weeks were selected.EAU model was established in 24 mice through immunization with the interphotoreceptor retinoid-binding protein (IRBP) 651-670.The 24 mice were sacrificed before immunization, and on the 3rd, 12th, and 18th day after immunization, with 6 at each time point.Flow cytometry was used to detect the proportion of IL-17A + interferon-γ (IFN-γ) + CD4 + T cells in the spleen, lymph nodes and eyeballs.Another 6 mice were selected to establish EAU model, and fundus images of the mice were taken with a small animal imaging instrument and optical coherence tomography (OCT) 18 days after immunization.The 6 mice were sacrificed after OCT examination and the eyeballs were collected.Hematoxylin-eosin staining was used to observe the retinal inflammation and morphological changes in tissue structure.Flow cytometry was employed to detect the proportion of IL-17A + IFN-γ + CD4 + T cells in lymph nodes.The 6 mice were divided into IL-17A + IFN-γ + highly expressed group and IL-17A + IFN-γ + lowly expressed group according to flow cytometry results, and the retinal injury was compared between the two groups.EAU model was established in another 36 mice, which were divided into anti-IL-12/IL-23 p40 group and IgG group by random number table method, with 18 mice in each group.Anti-IL-12/IL-23 p40 or IgG was injected by tail vein at a 3-day inteval according to grouping.On the 12th and 18th day after immunization, 6 mice were selected from each group to collect lymph nodes and eyeballs, and the proportion of T cell subsets was detected by flow cytometry.Eyeballs of 6 mice in each group were extracted on the 24th day after immunization and retinal damage was observed by hematoxylin-eosin staining.The induced differentiation of CD4 + T cells in vitro was assayed by flow cytometry.The expressions of IL-17 and IFN-γ were detected by enzyme-linked immunosorbent assay (ELISA) after induced differentiation of IL-17A + IFN-γ + CD4 + T cells.The relative expression levels of Th1 transcription factor T-bet and Th17 transcription factor retinoid acid-related orphan nuclear receptor γt (ROR-γt) after induced differentiation of IL-17A + IFN-γ + CD4 + T cells were detected by real-time quantitative PCR.The use and care of animals followed the ARVO statement and this study protocol was approved by an Ethics Committee of Experimental Animals of Tianjin Medical University Eye Hospital (No.TJYY2019111019). Results:There were significant differences in the proportion of IL-17A + IFN-γ + CD4 + T cells in lymph nodes, spleen and eyeballs between wild-type mice and EAU mice at the 3rd, 12th and 18th day after immunization ( H=9.642, 16.531, 10.385; all at P<0.05). Compared with before immunization, the proportion of IL-17A + IFN-γ + CD4 + T cells was significantly increased in lymph nodes of EAU mice on the 12th day following immunization and was significantly increased in spleen and lymph nodes on day 18 after immunization (all at P<0.05). Severe retinal exudation, retinal detachment, severe inflammatory cell infiltration and extensive retinal folds were detected in IL-17A + IFN-γ + highly expressed mice.Mild retinal edema, focal inflammatory cell infiltration and mild retinal folds were found in IL-17A + IFN-γ + lowly expressed mice.The proportion of CD3 and IL-17A + IFN-γ + CD4 + T cells in the eyeballs of anti-IL-12/IL-23 p40 group was lower than that in IgG group at the 18th day after immunization, and the differences were statistically significant ( t=15.304, 8.080; both at P<0.05). On day 12 after immunization, the percentage of IL-17A + IFN-γ + CD4 + T cells in anti-IL-12/IL-23 p40 group was (0.33±0.18)%, which was significantly lower than (4.83±0.45)% in IgG group ( t=15.974, P<0.001). Compared with IgG group, the percentage of Th1, Th17, IL-17A + IFN-γ + CD4 + T cells and the expression levels of IL-17, IFN-γ, T-bet, ROR-γt in anti-IL-12/IL-23 p40 group were significantly decreased, with statistical significances (all at P<0.05). Conclusions:Anti-IL-12/IL-23 p40 has a therapeutic effect on EAU by inhibiting IL-17A + IFN-γ + CD4 + T cells.

Current state and progress of intravitreal injection of chemotherapeutic agents for the treatment of vitreoretinal lymphoma / 中华眼底病杂志

Primary vitreoretinal lymphoma (PVRL) is one of the most common type of primary intraocular lymphoma. The current treatment options include local ocular radiotherapy (radiotherapy), systemic chemotherapy (chemotherapy), local ocular chemotherapy, and combination therapy. The treatment options are different at different stages of PVRL, however, there is no uniform treatment guideline. Local ocular chemotherapy can make the drug reach effective therapeutic concentration in the eye, and it can be repeated many times. At the same time, it can avoid the adverse reactions caused by systemic medication or radiotherapy. It is an ideal choice for relieving ocular symptoms. At present, the mainstream ocular local chemotherapeutics are methotrexate (MTX) and rituximab (RTX). The basic consensus about the intravitreal injection of MTX (IVM) is the induction-consolidation-maintenance model, however, the time of each stage and frequency of IVM are diverse. The time interval of intravitreal injection of RTX is also variable, ranging from 1 time/week to 1 time/months and so on. Corneal epithelial lesions caused by frequent MTX injections and the higher recurrence rate after RTX treatment are the main reasons for changing the treatment plan. For patients with primary central nervous system lymphoma and PVRL, combined treatment with neurology department is necessary to save patient's lives, ophthalmology treatment relieves ocular symptoms and improves the patient's quality of life. For patients with PVRL alone without central nervous system involvement, ophthalmology treatment is necessary to control patient's eye symptoms, and close follow-up should be followed to find the involvement of the central nervous system in time, and then combined with neurological treatment to save patient’s lives.

Current state and progress of rapamycin in the treatment of non-infectious uveitis / 中华眼底病杂志

Glucocorticoids (GCS) are the main treatment for non-infectious uveitis (NIU). However, long-term GCS treatment may induce systemic side effects including hypertension, hyperlipidemia and diabetes. Patients may develop cataract, ocular hypertension or glaucoma because of topical application of GCS. Rapamycin (RAPA) exhibits immunosuppressive, antiangiogenic and antiproliferative effects. Animal experiments and clinical trials have shown that RAPA has therapeutic potential for NIU, especially the treatment of intravitreal injection. In particular, intravitreal injection of RAPA can result in minimal systemic exposure and reduce adverse events. Meanwhile, systemic unwanted effects should be concerned about. In recent years, some studies have attempted to employ nanostructured carriers to improve penetrating abilities of RAPA and efficacy of treatment for ocular posterior segment diseases. These carriers include micelles, liposomes, nanocrystals, polymeric nanoparticles, magnetic nanoparticles and so on. Whether they can load RAPA for treating NIU deserves further study and exploration.

Effect of butorphanol mixed with ropivacaine for erector spinae plane block on postoperative outcomes in patients undergoing thoracoscopic pulmonary lobectomy / 中华麻醉学杂志

Objective:To evaluate the effect of butorphanol mixed with ropivacaine for erector spinae plane block (ESPB) on postoperative outcomes in the patients undergoing thoracoscopic pulmonary lobectomy.Methods:Eighty patients of either sex, aged 35-64 yr, with body mass index of 19-30 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, undergoing elective thoracoscopic pulmonary lobectomy, were divided into 2 groups ( n=40 each) using a computer-generated random number table method: butorphanol mixed with ropivacaine for ESPB group (group EB) and ropivacaine for ESPB group (group E). ESPB was performed under ultrasound guidance in both groups.A mixture of 0.1% butorphano 1 ml and 0.375% ropivacaine 20 ml was injected in EB group, and 0.375% ropivacaine 20 ml was injected in E group.The other anesthesia methods were the same in the two groups.And target-controlled infusion was stopped and PCIA was performed at the end of skin suture in the two groups.The intraoperative consumption of remifentanil, first time to press an analgesia pump, requirement for rescue analgesia within 24 h after surgery, and occurrence of ESPB-related complications were recorded.Quality of Recovery-40 (QoR-40) scores were recorded at 7 days after surgery.Before induction of anesthesia (T 1) and at 24 h after operation (T 2), the peripheral venous blood samples were collected for determination of plasma interleukin-6 (IL-6) and IL-10 concentrations, and bedside pulmonary function test was performed, and FEV 1/FVC was calculated. Results:Compared with group E, the QoR-40 scores were significantly increased at 7 days after operation, FEV 1/FVC was increased at T 2, the plasma concentrations of IL-10 were decreased at T 2, the plasma concentrations of IL-10 were increased at T 2, the intraoperative consumption of remifentanil was reduced, the first time to press an analgesia pump was prolonged, and the requirement for rescue analgesia within 24 h after surgery was decreased in group EB ( P<0.05). No ESPB-related complications were found in either group. Conclusion:Butorphanol mixed with ropivacaine for ESPB can improve postoperative outcomes in the patients undergoing thoracoscopic pulmonary lobectomy.

Effects of intravenous injection of human umbilical cord mesenchymal stem cells-derived small extracellular vesicles on experimental autoimmune uveitis in mice / 中华实验眼科杂志

Objective:To explore the therapeutic effects of intravenous injection of small extracellular vesicles (sEVs) derived from human umbilical cord mesenchymal stem cells (MSCs) on experimental autoimmune uveitis (EAU) in mice.Methods:MSCs from human umbilical cord were cultured and the supernatant was collected.The sEVs were isolated by ultracentrifugation method and a NanoSight instrument was used to analyze the particle size.The expression of surface markers sEVs, CD9, CD81 and CD63 was determined via Western blot.The morphology of sEVs was observed with a transmission electron microscope.Forty-eight 7-week-old female C57BL/6 mice were seclected to establish the EAU model through immunization with interphotoreceptor retinoid-binding protein peptide 651-670 (IRBP 651-670). The mice were divided into sEVs treatment group and phosphate buffer solution (PBS) control group using a random number table, with 24 mice in each group.The mice in the sEVs treatment group were injected with 50 μg of MSCs-derived sEVs via tail vein on the 11th day after modeling.In the PBS control group, the mice were injected with the same volume of PBS.Six mice in each group were randomly selected to observe the inflammation of the retina after mydriasis with an ophthalmoscope every other day from 8th day following modeling and the inflammation scores were evaluated.Six mice were randomly selected and sacrificed on the 14th day and 6 on the 18th day following modeling in each group, and both eyeballs of the mice were enucleated.Retinal tissue sections of the 6 mice sacrificed on the 18th day were stained with hematoxylin-eosin and the pathological scores were evaluated.The infiltration of helper T 1 (Th1) cells and Th17 cells in the eyeballs of the 6 mice sacrificed on the 18th day following modeling was detected by flow cytometry.T cells were isolated from spleen and lymph nodes of the 6 mice sacrificed on the 14th day, and the proliferation of T cells under different concentrations of IRBP 651-670 (0, 1, 10 and 20 μg/ml) was detected using a 5-bromodeoxyuridine (BrdU) method.To further study the effects of MSCs-derived sEVs on Th1/Th17 cells differentiation, naive T cells of spleen from another 3 normal mice were isolated by magnetic bead negative sorting and incubated with 10 μg/ml MSCs-derived sEVs or 10 μg/ml PBS, and then were cultured under Th1/Th17 cell differentiation conditions, respectively.Flow cytometry was used to measure the differentiation of naive T cells into Th1/Th17 cells.This study protocol complied with the regulations of the care and use of laboratory animals in China and was approved by an Ethics Committee of Tianjin Medical University (No.TJYY2019103022). Results:The isolated human MSCs-derived sEVs was with an average diameter of (102.4±33.6) nm and showed a double-layer membrane vesicle structure under the transmission electron microscope.The CD9, CD63 and CD81 proteins were highly expressed in sEVs.The inflammation scores of the sEVs treatment group were significantly lower than those in the control group on day 14, 16, 18, 20 and 22 after modeling (all at P<0.05). The pathological score of mice in the sEVs treatment group was significantly lower than that of PBS control group on the 18th day following modeling ( P<0.05). The flow cytometry results showed that on day 18 after modeling, the proportions of Th1 and Th17 cells in eyeballs in the sEVs treatment group were (15.55±2.03)% and (15.67±2.15)%, respectively, which were significantly lower than (21.35±0.72)% and (20.90±1.10)% in the PBS control group ( t=6.58, 5.31; both at P<0.01). BrdU results showed that when the IRBP 651-670 concentration was 20 μg/ml, the T cell proliferation ability in the sEVs treatment group was inhibited obviously compared with the control group ( P<0.05). The proportions of naive T cells differentiated into Th1 cells and Th17 cells in the sEVs treatment group were (28.15±1.32)% and (11.60±2.23)% respectively, which were significantly lower than (31.58±1.75)% and (23.52±1.76)% of the PBS control group, and the differences were statistically significant ( t=3.93, 10.26; both at P<0.05). Conclusions:Intravenous injection of human umbilical cord MSCs-derived sEVs can reduce the inflammation in EAU mice.The mechanism may be related to inhibiting the differentiation of naive T cells to Th1 and Th17 cells, and reducing the infiltration of Th1 and Th17 cells in the eyeballs.

Quantitative proteomic analysis of human umbilical cord mesenchymal stem cells with pigment epithelium-derived factor gene modification mediated by lentivirus / 中华实验眼科杂志

Objective:To investigate the protein expression changes of human umbilical cord mesenchymal stem cells (hUCMSCs) modified with pigment epithelium-derived factor ( PEDF) gene mediated by lentivirus. Methods:The hUCMSCs were divided into the control group and experimental group.Cells in the control group were normal hUCMSCs and the cells in experimental group were hUCMSCs with PEDF modification.The proteins from the two groups were collected and processed by FASP method.Samples were fractionated by liquid chromatography and analyzed by tandem mass spectrometry, and SWATH mode was applied.Differential protein analysis, Gene Ontology (GO) analysis and Reactome pathway enrichment analysis were performed. Results:A total of 5 361 quantified proteins were detected in this experiment, of which 432 proteins were differentially expressed (fold change>1.5, P<0.05). There were 219 of the 432 proteins up-regulated, including serpin family F member 1 (SERPINF1) (PEDF), DEAD-box helicase 59 (DDX59) and thrombospondin 1 (THBS1), etc., whereas 213 proteins were down-regulated, including collagen type Ⅰ alpha 1 (COL1A1), COL18A1, etc.GO analysis indicated that the differential proteins were mainly involved in fibrinolysis, extracellular structure organization, regulation of transporter activity, biosynthetic process of secondary alcohol and cholesterol, coenzyme metabolic process and regulation of peptidase activity, etc.Reactome pathway analysis showed that the differential proteins were mostly involved in regulation of insulin like growth factor (IGF) transport and uptake by IGF binding protein, post-translational protein phosphorylation, extracellular matrix organization, metabolism of steroids. Conclusions:After gene modification with PEDF mediated by lentivirus, the expression of many proteins in hUCMSCs were changed. PEDF gene modification can alter the structure of extracellular matrix and regulate the expression of proteins associated with cell proliferation, self-renewal and multipotency.